1. Field of the Invention
The present invention relates generally to a novel promoter gene, which is derived from Marek's disease virus (MDV) and can express two foreign genes in a recombinant turkey herpesvirus (HVT). More specifically, the present invention provides a recombinant HVT having the novel promoter gene between the two foreign genes, at least one of which is derived from a pathogen of avian infectious disease, and a poultry vaccine consisting of the recombinant turkey herpesvirus.
2. Description of the Related Art
Virus-vectored vaccines such as recombinant fowl pox viruses (FPV) or recombinant HVT have been already used in the poultry industry in the USA. In particular, live HVT vaccine is safe and efficacious against Marek's disease, and can be injected in ovo, which is suitable for mass vaccination of poultry flocks.
Because HVT is propagated through cell-to-cell infection, it is relatively free from the influences of anti-HVT specific antibodies present in the circulating blood. Therefore, the HVT live vaccine has a good character exhibiting its full effect even in the case of the presence of maternal antibody, which often attenuates the efficacy of a live vaccine.
It is well known that the genus herpesvirus, which includes HVT, has a property of permanently surviving in the body of an infected animal in the state of latent infection or persistent infection, and as a result, herpesvirus has the excellent vaccine character that it can raise a long duration immunity to a immunized animal.
Recombinant HVT vaccines have been reported (Japanese Patent No. 3587065, U.S. Pat. No. 7,153,511). Recombinant HVTs (HF006 and HF007) having multiple foreign genes such as HN and F genes derived from Newcastle disease virus (NDV), and VP2 gene derived from Infectious bursal disease virus (IBDV) were described in Japanese Patent No. 3587065, and they can express these foreign genes and elicit immunity to vaccinated chickens.
However, these recombinant HVT expressing multiple foreign genes were in most cases unstable, and all or a part of the foreign genes inserted in their genome are deleted during repeating passaging in culture cells.
As a result of intensive study to solve the above problems, the inventors of the present invention have found that bi-directional promoters derived from MDV can be useful for recombinant HVT, and that a recombinant HVT that is an HVT into the genome of which an expression cassette comprising two different foreign genes under control of the bi-directional promoter is inserted, can be very stable, such that the inserted foreign genes are not deleted, and are useful for poultry vaccines.